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Original Investigation
December 12, 2018

Association of Antipsychotic Treatment With Risk of Unexpected Death Among Children and Youths

Author Affiliations
  • 1Department of Health Policy, Vanderbilt University School of Medicine, Nashville, Tennessee
  • 2Division of Rheumatology, Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee
  • 3Division of Clinical Pharmacology, Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, Tennessee
  • 4Division of Cardiology, Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee
  • 5Department of Psychiatry and Behavioral Science, Vanderbilt University School of Medicine, Nashville, Tennessee
  • 6Department of Pediatrics, Vanderbilt University School of Medicine, Nashville, Tennessee
  • 7Vanderbilt Center for Child Health Policy, Vanderbilt University School of Medicine, Nashville, Tennessee
JAMA Psychiatry. 2019;76(2):162-171. doi:10.1001/jamapsychiatry.2018.3421
Key Points

Question  Are antipsychotic medications prescribed for children and youths without psychosis associated with increased risk of unexpected death or deaths other than from injuries or suicides without prolonged hospitalization?

Findings  In this cohort study of 247 858 Medicaid-enrolled children and youths in Tennessee who were new users of antipsychotic or control medications, the group that received a higher dose of antipsychotic medication had a significantly increased risk of unexpected death compared with the group that received control medication.

Meaning  This study suggests that antipsychotic treatment may be associated with increased mortality among children and youths and appears to underscore recommendations for careful medication use and monitoring in this population.

Abstract

Importance  Children and youths who are prescribed antipsychotic medications have multiple, potentially fatal, dose-related cardiovascular, metabolic, and other adverse events, but whether or not these medications are associated with an increased risk of death is unknown.

Objective  To compare the risk of unexpected death among children and youths who are beginning treatment with antipsychotic or control medications.

Design, Setting, and Participants  This retrospective cohort study was conducted from 1999 through 2014 and included Medicaid enrollees aged 5 to 24 years in Tennessee who had no diagnosis of severe somatic illness, schizophrenia or related psychoses, or Tourette syndrome or chronic tic disorder. Data analysis was performed from January 1, 2017, to August 15, 2018.

Exposures  Current, new antipsychotic medication use at doses higher than 50 mg (higher-dose group) or 50 mg or lower chlorpromazine equivalents (lower-dose group) as well as control medications (ie, attention-deficit/hyperactivity disorder medications, antidepressants, or mood stabilizers) (control group).

Main Outcomes and Measures  Deaths during study follow-up while out of hospital or within 7 days after hospital admission, classified as either deaths due to injury or suicide or unexpected deaths. Secondary outcomes were unexpected deaths not due to overdose and death due to cardiovascular or metabolic causes.

Results  This study included 189 361 children and youths in the control group (mean [SD] age, 12.0 [5.1] years; 43.4% female), 28 377 in the lower-dose group (mean [SD] age, 11.7 [4.4] years; 32.3% female), and 30 120 in the higher-dose group (mean [SD] age, 14.5 [4.8] years; 39.2% female). The unadjusted incidence of death in the higher-dose group was 146.2 per 100 000 person-years (40 deaths per 27 354 person-years), which was significantly greater than that in the control group (54.5 per 100 000 population; 67 deaths per 123 005 person-years) (P < .001). The difference was primarily attributable to the increased incidence of unexpected deaths in the higher-dose group (21 deaths; 76.8 per 100 000 population) compared with the control group (22 deaths; 17.9 per 100 000 population). The propensity score–adjusted hazard ratios were as follows: all deaths (1.80; 95% CI, 1.06-3.07), deaths due to unintentional injury or suicide (1.03; 95% CI, 0.53-2.01), and unexpected deaths (3.51; 95% CI, 1.54-7.96). The hazard ratio was 3.50 (95% CI, 1.35-9.11) for unexpected deaths not due to overdose and 4.29 (95% CI, 1.33-13.89) for deaths due to cardiovascular or metabolic causes. Neither the unadjusted nor adjusted incidence of death in the lower-dose group differed significantly from that in the control group.

Conclusions and Relevance  The findings suggest that antipsychotic use is associated with increased risk of unexpected death and appear to reinforce recommendations for careful prescribing and monitoring of antipsychotic treatment for children and youths and to underscore the need for larger antipsychotic treatment safety studies in this population.

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